Research Paper Volume 15, Issue 2 pp 553—566

Alterations of mesenchymal stem cells on regulating Th17 and Treg differentiation in severe aplastic anemia

Ju-Pi Li1,2, , Kang-Hsi Wu2,3, , Wan-Ru Chao1,4, , Yi-Ju Lee1,4, , Shun-Fa Yang5,6, , Yu-Hua Chao2,3,7, ,

  • 1 Department of Pathology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan
  • 2 Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan
  • 3 Department of Pediatrics, School of Medicine, Chung Shan Medical University, Taichung, Taiwan
  • 4 Department of Pathology, Chung Shan Medical University Hospital, Taichung, Taiwan
  • 5 Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
  • 6 Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
  • 7 Department of Clinical Pathology, Chung Shan Medical University Hospital, Taichung, Taiwan

Received: September 15, 2022       Accepted: January 23, 2023       Published: January 30, 2023      

https://doi.org/10.18632/aging.204500
How to Cite

Copyright: © 2023 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Immune-mediated hematopoietic destruction is a key factor in idiopathic severe aplastic anemia (SAA). With great immunomodulatory functions, mesenchymal stem cells (MSCs) are important for bone marrow niche. While the underlying etiology of immunologic changes in SAA bone marrow remains unknown, dysfunctional MSCs are implicated as a major cause. To provide evidence for their defects in immunomodulation, alterations of SAA MSCs in regulating T cell differentiation were determined. During differentiation from CD4+ T cells into T helper 17 (Th17) cells under polarization conditions, impaired inhibition on IL-17 and IL-1β production was noted when cocultured with SAA MSCs compared to control MSCs (P < 0.05). After stimulation of Th17 activation, the percentage of IL-17-secreting cells was significantly increased in the SAA group (9.1 ± 1.5% vs 6.6 ± 0.4%, P < 0.01). Under regulatory T (Treg) polarization, a higher percentage of CD4+CD25+FoxP3+ Treg cells was detected when cocultured with SAA MSCs compared to control MSCs (8.1 ± 0.5% vs 5.8 ± 0.8%, P < 0.01). Inconsistently, transforming growth factor-β (TGF-β) concentrations in the culture supernatant were decreased and IL-1β concentrations were elevated in the SAA group. Our data indicated impaired inhibition of SAA MSCs on Th17 activation and aberrant regulation of SAA MSCs on Treg differentiation. Increased IL-17 and IL-1β levels with decreased TGF-β levels in the supernatant suggested the potential of SAA MSCs for triggering a hyperinflammatory environment. Dysfunctional MSCs could contribute to the lack of immunoprotection in the bone marrow, which may be associated with SAA.

Abbreviations

APC: allophycocyanin; FBS: fetal bovine serum; FITC: fluorescein isothiocyanate; HSCs: hematopoietic stem cells; IFN-γ: interferon-γ; MSCs: mesenchymal stem cells; PE: phycoerythrin; SAA: severe aplastic anemia; TGF-β: transforming growth factor-β; Th17: T helper 17; TNF-α: tumor necrosis factor-α; Treg: regulatory T.